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The Grand Duchy of Hesse and by Rhine (German: Großherzogtum Hessen und bei Rhein), or, between 1806 and 1816, Grand Duchy of Hesse (German: Großherzogtum Hessen)—as it was also known after 1816—was a member state of the German Confederation from 1806, when the Landgraviate of Hesse-Darmstadt was elevated to a Grand Duchy, until 1918, when all the German monarchies were overthrown. Before 1866, its northern neighbour was its former sister Landgraviate, since 1803 an Electorate, of Hesse-Kassel – for this reason, this state was sometimes colloquially known as Hesse-Darmstadt.

The majority of the state combined with Frankfurt am Main, the Waldeck area (Rhine-Province) and the former Prussian province of Hesse-Nassau to form the new state of Hesse following the Second World War. Excluded were the Montabaur district from Hessen-Nassau and that part of Hessen-Darmstadt on the left bank of the Rhine (Rhenish Hesse), which became part of the Rhineland-Palatinate state. (Bad) Wimpfen—an exclave of Hessen-Darmstadt—became part of Baden-Württemberg, in the district of Sinsheim. After the vote, Bad Wimpfen was transferred from Sinsheim district to Heilbronn one in 29 April 1951. This change to Heilbronn was carried out on May 1, 1952.